[BRAF gene mutation in thyroid cancer]

Mutations of genes coding effectors of signaling pathway RET/PTC-RAS-RAF-MEK-ERK, involved in cell growth and proliferation, are important in papillary thyroid cancer development. To earlier discovered mutations of RAS and RET/PTC genes, BRAF gene mutation has been recently added. Mutation of BRAF gene appears in various types of carcinomas, but most frequently in malignant melanomas (66%) and papillary thyroid cancer (average 44%). The BRAF gene protein product belongs to the serine-threonine kinase family and to the RAF proteins subfamily, among which it is the strongest activator of MAP kinases cascade. The most frequently mutation of BRAF gene is thymine to adenine transversion at nucleotide position 1796 (T1796A). This point mutation causes valine to glutamic acid substitution at residue 599 (V599E), that results in constitutive and oncogenic activation of BRAF kinase. The relation between mutations of BRAF, RAS and RET/PTC genes has not been found, although they together exist in two thirds of papillary thyroid cancers. BRAF(TI796A) oncogene appears in papillary thyroid cancer, whereas it has not been found in follicular thyroid cancer and benign thyroid adenomas. For this reason mutated BRAF gene could be specific molecular marker, with relatively high sensitivity in diagnostics of papillary thyroid cancer. In addition, BRAF gene has been demonstrated as a novel prognostic biomarker, which correlates with unfavorable clinicopathological factors, such as extrathyroidal invasion and distant metastasis.